Project Summary ? OVERALL The goal of the proposed COBRE program is to create an Integrative Center for Environmental Microbiomes and Human Health (ICEMHH) in response to the 2016 announcement of the National Microbiome Initiative (NMI). The NMI was conceived through the recognition that humans are both connected to and reliant upon the microbial communities that constitute the Earth's microbiomes, in the environment as well as the human body. The NIH plays a central role in funding this effort, ?..with a particular emphasis on multi-ecosystem comparison studies, and investigation into the design of new tools to explore and understand microbiomes? [NIH Human Microbiome Project]. The focus of ICEMHH is the interface between the microbial environment and human health, and spans state-of-the-art `-omics' methods to ecological analyses and predictive models. The University of Hawai?i brings three compelling strengths to microbiome research: the uniquely tractable and scalable landscape of the Hawaiian Islands, an exceptionally qualified biology faculty, including an integrated cohort of recently hired, microbiome-focused, tenure-track, junior professors, and a dedication to the diversity of people that live on the Islands. As the most diverse biome on Earth, Hawai?i offers the opportunity to study the effects of ecological gradients on human health, from mountain to sea, and in both urban and rural settings. The proposed projects aim to address two critical and intertwined health problems: the deteriorating environment, and the current spread of insect-vector borne diseases. In this context, proposed research efforts will (i) explore how human health is impacted by exposure to pathogenic microbes in the environment; (ii) examine how the microbiomes of insect vectors affect their transmission of disease within the microcosm of the island of O?ahu; and, (iii) exploit invertebrate models to provide insight into the underlying cellular, genetic and molecular mechanisms by which microbiomes confer health. In this way, the Center will provide lasting contributions to the State of Hawai?i, and beyond.